Health Outcomes Research

Survey of Overactive
Bladder Symptoms Influencing
Bother Before and After Treatment With
Tamsulosin Hydrochloride in Japanese
Patients With Benign Prostatic Hyperplasia
Akira Tsujimura, Tetsuya Takao, Yasushi Miyagawa, Hidenobu Okuda,
Keisuke Yamamoto, Shinichiro Fukuhara, Jiro Nakayama, Tomohiro Ueda, Hiroshi Kiuchi,
Toshiaki Hirai, Yuichi Tsujimoto, Hidenobu Miura, Nobuteru Kanno, Makoto Higashino,
Yoshihiro Nakamura, Kenji Nishimura, and Norio Nonomura
OBJECTIVE To evaluate the relation between bother and overactive bladder (OAB) symptoms in patients
with benign prostatic hyperplasia (BPH) patients using questionnaires: the BPH Impact Index
(BII) and the OAB symptom score (OABSS). Annoyance from BPH usually provides the basis
for a patient’s decision to seek medical treatment. However, a study investigating the bother
caused by OAB symptoms in patients with BPH and OAB has not been fully conducted.
METHODS The present study included 100 male patients who were diagnosed with BPH and OAB according
to questionnaire criteria. All patients were instructed to take tamsulosin for 28 days. The relation
between the BII and OABSS was assessed to determine the factors influencing OAB symptoms
on the BII before and after treatment.
RESULTS The BII correlated positively with the OABSS, and multivariate analysis showed that the
subscore of urgency was the only independent factor influencing the BII. Even after treatment,
lower urinary tract symptoms were diagnosed as OAB using the OABSS criteria in 45 (45.0%)
of the 100 patients. In these patients, the BII still correlated positively with the OABSS.
However, multivariate analysis showed that the subscore of urgency incontinence, not urgency,
was the only independent factor influencing the BII, although the subscore of urgency inconti-
nence was significantly decreased with tamsulosin treatment.
CONCLUSION The degree of bother correlated with the degree of OAB symptoms in patients with BPH and
OAB at baseline and after treatment with tamsulosin. The OAB symptom causing the bother was
altered by treatment with tamsulosin in these patients. UROLOGY 78: 1058 –1062, 2011. © 2011
Elsevier Inc.

B
enign prostatic hyperplasia (BPH) is a common
health problem in aging men, affecting 50%-80%
of men aged 40-80 years.1 However, its clinical
symptoms are rarely life-threatening. The degree to
which symptoms become bothersome or worrisome to
patients with BPH and disrupt daily activities usually
provides the basis for a decision to seek medical treat-
From the Department of Urology, Osaka University Graduate School of Medicine,
Suita, Osaka, Japan; Department of Urology, Saiseikai Senri Hospital, Suita, Japan;
Miura Clinic, Kashihara, Japan; Kanno Clinic, Sakai, Japan; Higashino Clinic,
Takarazuka, Japan; Department of Urology, Nakamura Clinic, Toyonaka, Japan; and
Department of Urology, Nishinomiya Prefectural Hospital, Nishinomiya, Japan
Reprint requests: Akira Tsujimura, M.D., Ph.D., Department of Urology, Osaka
University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka 565-0871
Japan. E-mail: akitsuji@uro.med.osaka-u.ac.jp
Submitted: April 2, 2011, accepted (with revisions): May 24, 2011
1058 © 2011 Elsevier Inc.
All Rights Reserved
ment.2,3 Some patients with severe symptoms experience
little discomfort or worry about their health, and other
men, with mild symptoms, are very bothered by them.4
This discrepancy indicates significance in the perception
of bother in the evaluation and treatment of patients
with BPH. Thus, the bother associated with BPH is a key
decision point in the diagnosis and treatment algorithm
of the 2003 American Urological Association guidelines
on managing BPH.5 The lower urinary tract symptoms
(LUTS) of BPH that relate to voiding tend to be more
prevalent, and the symptoms related to storage (eg, fre-
quency, nocturia, and incontinence) are embarrassing
and disruptive to daily life and tend to be more bother-
some.6 Recently, the concept of overactive bladder
(OAB), defined as a symptom syndrome characterized by
0090-4295/11/$36.00
doi:10.1016/j.urology.2011.05.032
urgency, with or without urgency incontinence, and usu-
ally including frequency and nocturia in the absence of
confirmed infection or other obvious pathologic find-
ings,7 has gained increasing attention in the field of
urology and public health with respect to patients’ quality
of life (QOL) as 1 of the representative storage symptom
diseases. It affects 14.0% of men aged ⱖ40 years in
Japan,8 15.6% of the same age group in Europe,9 and
16.0% of men aged ⱖ18 years in the United States10 and
is believed to be a bothersome condition that compro-
mises the QOL of those affected.11 Recently, the popu-
lation-based, cross-sectional survey (EPIC study) showed
that bother among men with OAB symptoms increased
with the number of LUTS reported and with the severity
of urgency.12 However, the study investigating which
OAB symptoms, such as urgency, urgency incontinence,
and nocturia, causes bother in patients with BPH and
OAB has not been fully conducted.
The BPH Impact Index (BII), a validated and useful
disease-specific questionnaire with only 4 questions, ad-
dressing physical discomfort, worry, level of bother, and
effect on normal activity, has been used to assess bother,
as well as treatment outcomes, in men with symptomatic
BPH.13 Furthermore, the OAB symptom score (OABSS)
has recently been developed to assess and diagnose
OAB.14 The OABSS is also a simple questionnaire with
4 questions that express the OAB symptoms collectively.
It has been used as a brief assessment tool for symptom
severity, as well as annoyance.14,15 In the present study,
we used the BII and OABSS to evaluate the relation
between bother and OAB symptoms in patients with
combined BPH and OAB.
MATERIAL AND METHODS
Participants
Included in the present study were 100 male patients (mean age
68.8 ⫾ 8.0 years) diagnosed with both moderate or severe BPH
(indicated by a total score of ⱖ8 on the International Prostate
Symptom Score [IPSS] and a score of ⱖ2 on the QOL index)
and OAB (indicated by the OABSS criteria of a total score of
ⱖ3 and a question 3 (Q3) (urgency) score of ⱖ2 (ⱖ1 week).14
No patient had taken medications, such as ␣-adrenoceptor
antagonists or anticholinergic drugs for LUTS caused by BPH,
OAB, or other etiologies. Patients were excluded if they had
been diagnosed with prostate cancer, undergone surgical treat-
ment of the prostate gland, had a urinary tract infection, expe-
rienced acute urinary retention within 4 weeks of the screening
visit, or had a history or evidence of urethral stricture or renal
dysfunction. All patients were instructed to take tamsulosin 0.2
mg orally each morning approximately 30 minutes after break-
fast for 28 days. Their bother and OAB symptoms were assessed
using the BII and OABSS, respectively, before and after treat-
ment.
Methods
At the pretreatment baseline, the relation between the BII and
OABSS in our subjects was assessed. The relation between the
BII and OABSS was assessed again in the population of patients
UROLOGY 78 (5), 2011
whose LUTS was diagnosed as OAB using the OABSS criteria
even after treatment. At baseline and after treatment, the
OABSS factors with an influence on the BII were also inves-
tigated. Finally, the change in Q3 (urgency) and Q4 (urgency
incontinence) scores from the OABSS was analyzed in the
population of patients whose LUTS was diagnosed as OAB
using OABSS criteria even after treatment.
Statistical Analysis
The relation between the BII and OABSS was investigated
with Pearson’s correlation coefficient. Factors with an influence
on the BII were investigated among the 4 parameters of the
OABSS (ie, frequency, nocturia, urgency, and urgency incon-
tinence) using multivariate analysis. A comparison of the 2
groups was performed using the Wilcoxon signed rank test. P ⬍
.05 was considered statistically significant.
RESULTS
Relation Between BII and OABSS
The BII correlated positively with the OABSS for all 100
patients with BPH and OAB at baseline (Pearson’s cor-
relation 0.467, P ⬍ .001; Fig. 1A). Among them, LUTS
was diagnosed as OAB, according to the OABSS criteria,
in 45 patients (45.0%) even after treatment with tamsu-
losin. The BII still correlated positively with the OABSS
for these 45 patients after treatment (Pearson’s correla-
tion 0.547, P ⬍ .001; Fig. 1B).
OABSS Factors With Influence on BII
Of the 4 OABSS subscores, multivariate analysis showed
that the subscore of urgency was the only independent
factor influencing the BII for the 100 patients with BPH
and OAB at baseline (Table 1). Multivariate analysis also
showed that only the subscore of urgency incontinence,
and not urgency, was an independent factor influencing
the BII for the 45 patients whose OAB remained after
treatment (Table 1).
Change in OABSS Q3 and Q4 Scores
in Patients With OAB Persisting After Treatment
The subscore of urgency (Q3), which was an indepen-
dent factor influencing the BII at baseline, was signifi-
cantly decreased by treatment for the 45 patients whose
OAB remained after treatment (Fig. 2A). The subscore
of urgency incontinence (Q4), an independent factor
influencing the BII after treatment, was also significantly
decreased by treatment for these patients (Fig. 2B).
COMMENT
BPH is highly prevalent among elderly men. Because the
pathogenesis of BPH is thought to involve not only lower
urinary tract obstruction, but also bladder dysfunction, its
clinical signs and symptoms are complicated and often
vary among patients.16 Generally, the LUTS associated
with BPH comprise not only voiding symptoms, but also
storage symptoms. Regarding the extent of the interac-
tion between BPH and OAB, a previous study reported
1059
Figure 1. Relation between OABSS and BII in (A) 100 patients with BPH and OAB at baseline and (B) 45 patients whose
symptoms of OAB remained after treatment with tamsulosin. Statistical analyses were performed using Pearson’s corre-
lation coefficient.

Table 1. Multivariate analysis of factors influencing Be- symptoms increased with the number of LUTS re-
nign Prostatic Hyperplasia Impact Index in patients with ported and with the severity of urgency.12 The OABSS
benign prostatic hyperplasia and overactive bladder at is a validated, self-assessment questionnaire consisting
baseline and after treatment of 4 questions on OAB symptoms, but it places more
Regression weight on the scores for urgency and urgency inconti-
Symptom Coefficient t Value P Value nence than on the other 2 scores according to the
Baseline clinical setting. Patients respond to each question
Frequency 0.038 0.536 NS about their bladder symptoms during the previous
Nocturia 0.029 0.427 NS week. Recently, it was proved that the OABSS is
Urgency 0.460 6.847 ⬍.01
Urgency incontinence 0.119 1.454 NS highly sensitive to treatment-related changes in OAB
After treatment symptoms in a study comparing the OABSS and a
Frequency 0.139 1.029 NS bladder diary as a combined tool for assessing OAB
Nocturia 0.200 1.500 NS symptoms.20 In addition to the IPSS and QOL index,
Urgency ⫺0.003 ⫺0.019 NS
the American Urological Association also recom-
Urgency incontinence 0.467 3.463 ⬍.01
mends the BII as a questionnaire for the assessment of
NS, not significant. LUTS/BPH.5 Thus, we investigated the bother related
to OAB symptoms in patients with BPH and OAB
that OAB, diagnosed by the urodynamic presence of using these reliable questionnaires, the OABSS and
involuntary detrusor contractions of ⱖ10 cm H2O, was BII.
found in 47% of patients with bladder outlet obstruction In the present study, we showed that the degree of
secondary to BPH.17 However, it is well known that bother correlates with the degree of OAB symptoms in
involuntary detrusor contractions are not always found at patients with combined BPH and OAB at baseline and
the urodynamic examination in all patients with OAB. after treatment with tamsulosin (Fig. 1). Multivariate
We previously reported that the prevalence of OAB was analysis revealed that the OAB symptom that primarily
55.9% in Japanese patients with BPH according to a determined the BII was urgency (Table 1). Urgency is
questionnaire-based survey with the IPSS and OABSS.18 essential for the diagnosis of OAB according to the
To date, several reports have been published regarding definition of the International Continence Society7 and
the relation between OAB symptoms and QOL. It was is thought to be central in driving all other OAB symp-
reported that OAB is associated with both a clinically toms, including frequency, nocturia, and urgency incon-
and a statistically significantly lower score on the Medical tinence. It is also well known that urgency has a signif-
Outcomes Study 36-Item Short-Form Health Survey, in- icant negative effect on health-related QOL.21,22
creased depression, and poor sleep quality.10 Recently, we Recently, we also reported that urgency and nocturia are
also found a close relation between OAB symptoms and factors that independently affect sleep quality, which is
sleep efficiency in a study using the OABSS and poly- closely related to patients’ QOL.19 Thus, it is easily
somnography.19 However, the level of bother caused by accepted that the key symptom causing bother is urgency
OAB symptoms has not been fully investigated. Only the in patients with combined BPH and OAB. However, the
EPIC study showed that bother among men with OAB most interesting finding in the present study was that the

1060 UROLOGY 78 (5), 2011

Figure 2. Change in scores for (A) Q3 (urgency) and (B) Q4 (urgency incontinence) of OABSS after treatment with
tamsulosin in 45 patients whose symptoms of OAB remained after treatment. Statistical analyses were performed using
Wilcoxon signed rank test.
independent factor influencing the BII obtained by mul-
tivariate analysis was urgency incontinence, and not ur-
gency, after treatment of patients whose OAB remained
even after the treatment with tamsulosin (Table 1).
Tamsulosin, a combined ␣-1A and ␣-1D adrenoceptor
antagonist, has been used as the global standard for the
treatment of BPH. It was reported that uroflow is im-
proved within 4-8 hours of administration, and the total
American Urological Association Symptom Scores are
improved after 4 days of treatment.23 Other studies have
shown good efficacy, as well as tolerability of tamsulo-
sin.24-27 Furthermore, tamsulosin exerts a relaxant effect
on urethral smooth muscle. It has been speculated that
tamsulosin exerts an inhibitory effect on C-fiber urethral
afferent nerves by decreasing urethral tonus and improv-
ing blood flow to the bladder, thereby improving storage
symptoms, such as OAB. We previously reported that the
total score and all subscores of the OABSS, as well as the
IPSS and QOL index, were significantly improved after
treatment with tamsulosin 0.2 mg/d for only 4 weeks.18
We, and others, also reported significant improvement in
the BII with tamsulosin treatment.18,28,29 The dose of
tamsulosin used in our present and previous studies18 was
0.2 mg/d, which is usual in Japan, because tamsulosin 0.4
mg/d is not permitted in Japan. We know that this is
lower than that used in Western countries. However, our
results provide evidence for the usefulness of tamsulosin
for OAB, despite this lower dose.
One possibility to explain why the most bothersome
symptom was changed by tamsulosin treatment is that
patients find urinary incontinence more bothersome after
treatment owing to the improvement in bladder neck
obstruction caused by the action of tamsulosin. However,
this hypothesis is obviously denied because urgency in-
continence is, instead, improved by tamsulosin treatment
as shown by the significant decrease in the OABSS Q4
score after treatment in patients with BPH and OAB
UROLOGY 78 (5), 2011
(Fig. 2B). A large-scale study of patients with LUTS
suggestive of BPH showed that when present, urinary
incontinence appeared highly bothersome, even though
it was experienced by a minority of the study population,
although the “rush to toilet” (urgency) was most common
among the storage symptoms.30 In our patients with
combined BPH and OAB after treatment, that tamsulo-
sin was effective for urgency is shown in the significant
decrease in the OABSS Q3 score (Fig. 2A). If the degree
of urgency as a common symptom is reduced even
slightly, urgency incontinence as a highly bothersome
symptom may then come to the forefront of the patient’s
perception. In the present study, the BII score decreased
in patients whose OAB symptoms improved after treat-
ment (6.3-2.7) and those whose OAB symptoms did not
improve after treatment (7.2-4.3). The BII was signifi-
cantly greater in patients with OAB than in those with-
out OAB after treatment (data not shown). This specu-
lation regarding the severity of bother might explain the
reason why patients with combined BPH and OAB are
bothered by urgency before treatment and urgency in-
continence after treatment. That frequency and nocturia
were not influencing factors on the BII either before or
after treatment might also have been an artifact of sample
size. An additional large-scale study would be necessary
to clarify this point.
CONCLUSIONS
In the present study, we showed that bother correlates
with OAB symptoms in patients with BPH and OAB and
that the OAB symptom causing bother was changed by
tamsulosin treatment in these patients. It is important for
physicians to pay attention to these findings, especially
the change in bother symptoms, when considering treat-
ment of combined BPH and OAB.
1061
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UROLOGY 78 (5), 2011